This is the first competing renewal application for a Program Project to support and expand interactions that focus on the signaling mechanisms that control the directed outgrowth of neuronal processes and the directed movement of neuronal cells. Together these two properties are essential to neuronal function, since the precise location of neurons and proper interconnection of their axons and dendrites underpins all neuronal signaling and plasticity. Abnormal patterns of neuronal migration have been implicated in human neurological disorders associated with mental retardation, epilepsy, and dyslexia, while congenital disorders of mental retardation are increasingly recognized as having major disorders of axonal and dendritic connections. Project 1, headed by Christopher Walsh, focuses on the analysis of genes implicated in neuronal migration and process outgrowth based on human genetic studies. Project 3, headed by John Flanagan, focuses on mechanisms of action of neural guidance factors in animal models. Project 2, headed by Davie Van Vactor, focuses on analysis of genes that control axon guidance in Drosphila, some of which correspond to human disease genes. There are two cores, one of which is dedicated to supporting state-of-the-art imaging.